DESCRIPTION: (Adapted from the applicant's abstract.) The overall objective of this project is to define the contribution of systemic organ injury to the abnormalities that occur in oxygen uptake-oxygen delivery relations in conditions that lead to the adult respiratory distress syndrome (ARDS). In this regard, ARDS is most often a syndrome of lung and systemic organ injury that is caused by the activation of circulating inflammatory cells and/or the release of humoral mediators. In some situations (for example, bacterial infection), the stimulus for inflammation may cause simultaneous organ and lung injury while in other situations (that is, gastric aspiration) systemic organ injury may be minimal insofar as the lung is the primary target organ. In either situation, one poorly understood observation is the loss of the normal relationship between oxygen uptake (VO2) and oxygen delivery (QO2) that occurs in ARDS. The nature of the injury within individual organs and the quantitative degree to which they contribute to whole body VO2-QO2 derangements has not been delineated. The purpose of this project, therefore, is to test the hypothesis that: systemic organ injury is the underlying cause of the abnormalities in oxygen uptake-oxygen delivery relationships that occur in conditions that lead to the ARDS. The first aim will be to demonstrate that only forms of acute lung injury which are caused by or result in circulating inflammatory cell activation will result in whole body VO2-QO2 abnormalities. Organ injury will be defined in these studies by morphologic abnormalities and organ edema formation; and, the studies will be performed animals with contrasting forms of acute lung injury (that is, phorbol myristate acetate [PMA]-induced acute lung injury and acid aspiration lung injury). The second aim will be to establish that endothelial injury in individual systemic organs during acute lung injury is the cause of individual organ VO2-QO2 abnormalities. Endothelial injury in these individual systemic organs will be assessed by morphologic abnormalities and by abnormalities in microvascular protein permeability and fluid flux. With respect to both aims, it is postulated by the investigators that activated inflammatory cells (that is, the neutrophil) provide the link between the acute lung injury and the ultimate development of systemic organ injury and VO2-QO2 abnormalities. Namely, the stimulus for acute lung injury either directly or indirectly causes inflammatory cell activation. To the extent that this occurs, systemic organ injury occurs and results in VO2-QO2 abnormalities.